A molecular “spring” protects our hearing from damage

A new study published in PNAS highlights a newly identified mechanism of auditory sensitivity regulation that may temporarily reduce the sensitivity of the auditory system to protect against loud sounds that can cause irreversible damage.

The study, led by CU Anschutz researchers Andrew Mecca and Giusy Caprara in Anthony Peng’s lab, tested a decades-old hypothesis that proposed that the trigger spring, a tiny nanoscale protein structure that Mechanically opens and closes an ion channel in sensory hair cells in response to sound vibrations, can act directly as a controller of channel activity.

Previous work in the auditory field has primarily focused on understanding the mechanisms that target the ion channel. This study provides the first evidence that the trigger spring itself has the ability to modulate channel sensitivity.

“This study documents the first time that we understand a mechanism that regulates hearing sensitivity at the molecular and mechanical levels,” says Peng, Ph.D., associate professor at the University of Colorado School of Medicine and lead author of the study. ‘study. “We have discovered a new mechanism for modulating sensitivity, which opens the door to uncovering how the auditory system generally works and using it to both maximize the range of sounds we can detect and protect vital sensory cells from potential damage.”

The mechanism discussed in the study works by altering a physical property of the trigger spring, its stiffness, which is responsible for controlling the opening and closing of the canal in response to sound vibrations entering the inner ear. The researchers studied the properties of the trigger spring and the resulting channel activity in single sensory hair cells, and found that cyclic adenosine monophosphate (cAMP), a specific type of signaling molecule, reduced the stiffness of the spring. tripping and decreased channel capacity. sensitivity – which is the first time that a physiological mechanism for controlling trigger spring stiffness has been identified.

“Identifying the underlying mechanism of this process – how it works physiologically and mechanically, paves the way for future research and provides an opportunity for the field to develop a new type of drug that can be used to prevent a type of hearing loss. which occurs from exposure to very loud sound,” says Peng. Ultimately, they aim to find out more about how the ear can detect such a wide range of sounds and how the system protects itself, which is a huge step forward for the field.

Reference: Mecca AA, Caprara GA, Peng AW. cAMP and voltage modulate rat auditory mechanotransduction by decreasing the stiffness of trigger springs. PNAS. 2022;119(30):e2107567119. doi: 10.1073/pnas.2107567119

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